Infection with human cytomegalovirus (HCMV) is usually asymptomatic and self-limiting in the normal human population. However, it can cause serious infection if contracted in utero, leading to severe neurological handicaps and/or deafness in a significant number of cases. Moreover, HCMV is among the most common causes of morbidity and mortality in immunosuppressed patients and patients with immune deficiency diseases.
HCMV is a member of the family herpesvirdae, and is composed of a nuclear complex of nucleic acid and proteins surrounded by an external membrane envelope containing glycopeptides and glycolipids. Among the antigenically distinct envelope (glyco)proteins characterized by our laboratory and others, several are associated by disulfide bonds in high molecular weight complexes. Commonly assigned U.S. patent application Ser. No. 933,789, filed Nov. 24, 1986, entitled, "Immunogenic Glycopeptides of Human Cytomegalovirus" describes the isolation and characterization of antigenically related glycopeptides of molecular weights 93,000 daltons and 50,000-52,000 daltons. These glycoproteins were obtained by the reduction of a set of glycoprotein complexes having molecular weights of .gtoreq.450,000 daltons and 130,000-180,000 daltons. Moreover, two prototype murine monoclonal antibodies (mcAb) disclosed in the above patent, 41C2 and 9B7, immunoprecipitate these individual glycoproteins, as well as the antigenically-related glycoprotein complexes. McAb 9B7 also exhibits neutralizing activity against HCMV in vitro in the presence of complement. Convalescent sera from patients who have recovered from HCMV infection also contain antibodies that immunoprecipitate these HCMV glycoproteins, suggesting that antibodies reactive with these glycoproteins may participate in neutralization of virus in vivo.
Therefore, there is a need for HCMV-specific mcAbs that have practical clinical utility in the diagnosis and treatment of HCMV infections. A further needs exists for mcAbs that are useful both in direct detection of HCMV in clinical specimens and rapid identification of the virus in tissue culture. Such antibodies may be used either to capture and concentrate a viral antigen, or alternatively, for immunological detection of the virus using a variety of known immunoassay techniques. There is recent evidence suggesting that the administration of hyperimmune HCMV globulin to immunosuppressed patients prior to organ or bone marrow transplantation may possibly attenuate or prevent life-threatening HCMV infections in the post-transplant period. This same therapy may also be useful in treating patients who already have clinical illness due to HCMV. It is therefore possible that administration of murine mcAbs reactive with individual HCMV (glyco)proteins may also ameliorate the course of HCMV infection in these patients.